Imidazolines



Patented M, 1939 r 2,149,473

UNITED STATES PATENT OFFICE ILIIDAZOLINES Adolf Sonn, Konigsberg, Germany, 'assignor to the firm of Society of Chemical Industry in Basie, Basel, Switzerland No Drawing. Application September 10, 1937, Serial No. 163,324. In Germany July 31, 1934 3 Claims. (01. 269-309) The present application is a continuatlon-inheating the salts of aliphatic 1:2-dia'mines with part of my copending application Serial lfIo. salts of fatty acids ELadenburg, Berichte der 33,911, filed July 30,1935. deutschen Chem. Gesellschaft, vol. 2'7, pages It has been found that imidazolines of the 2952-57 (1894), Klingenstein, loco citato vol. 28,

5 general formula 7 pages 1175-76 (1895)]. 2-phenyl-imidazoline can 5 NCH, be obtained by causing thiobenzamide to react J with ethylene diamine EG. Forssel, loco citato vol. 25, pages 2132-42 (1892)] or by the action NH- of benzimino-ethylether on bromethylamine hy- Whereln R Stands for a member of the group (1011- drobromide in the presence of sodium alcoholate 10 Sisting 0f Substituted a un u t P y [Stoll et al-., Journal fiir praktische Chemie, nap y d q y ad ls, t su st nt vol. 140, page 60 (1934)]. Compounds of the being a member of e group st ng of alkyl, kind indicated above are also obtained by the a y v xy nd k xy d r vativ s and n action of iminoethers of higher fatty acids on stands for the numbers 1 to 6, can be obtained diamines [Bockmiihl et al., U. S. Patent 1,958,529 by causing iminoethers of the general formula (1934) Further it is known to obtain -glyox- NH alidine-arylmethylols by the action of alkylene diamines on iminoethers of substituted mandelic acids [Bockmiihl et al., U. S. Patent 1,999,989 7 R1 (1935) wherein R and n have the signification indicated Th n w compounds, th sal f whi h are all above and R1 stands for an alkyl radical, to react easily Soluble in Water, have essential p wlth ethylene diamine. cological advantages over the known compounds The iminoethers may be cau ed to react ith indicated above. Thus, for example the blood ethylene diamine in the form of free bases or as Pressure of the r bb t s increased to a much 25 salts of mineral acids, in the presence or absence greater extent. of a solvent such as alkanols or alkyl polyhalides The following table illustrates t high e ecat room temperature or at a, r i ed temperature, tiveness of compounds obtainable according to When the reaction is carried out at low temthe Present process;-

0 perature and particularly when using free iminoethers, a neutral gas is preferably passed through Minimal dose in the composition, for the purpose of removing the 553 533555; ammonia formed in the course of the reaction. Compound the blood pres- When using a free iminoether and in the absence si igs i l i d m- 5 of a solvent, the crude imidazoline is obtained directly after the reaction is at an end, which a be r nized by t dis inuat n of 3;lfttttttftt tiitiiiitilzfit???i'if:::1 313383501 evolution of ammonia. The crude imidazoline z-lnephthoxv-(ltmsthyliimidezeline (1000001 can be purified by distillation or crystallization.

40 When using however a salt of an iminoether as The following examples illustrate the invention, 40

well as a solvent, the solvent is distilled when the the parts being by weight: evolution of ammonia is finished, the residue is recrystallized or mixed with a strong lye, and extracted with an organic solvent insoluble in Hydrogen chloride is introduced into a cooled water. After drying the solution of the extracmixture of equimolecular quantities of 45 with of the usual alkaline f g agents, oxy-phenoxyacetonitrile and alcohol and the the solventlls expelled and the resldual mudazo' 2-methoxy-phenoxyacetimidoether-hydrochloride line base is either distilled or recrystallized. thus obtainedof the formula The iminoethers used as parent materials are Example 1 produced from the corresponding nitriles by dis- NIFHC 50 solving the latter in alkanols or in other organic 0GH solvents to which an alkanol has been added, 002m mixing them at low temperature with a mineral OCH:

acid and allowing them to stand for several hours. It is known to produce 2-a1kyl-imidazolines by is triturated with an indifferent solvent, such as 55 petroleum ether, ether or benzene. It isobtained in the form of a colorless crystalline powder sensitive to moisture.

24.5 parts of this imidoether-lrvdrochloride are mixed with 6.5 parts of ethylenediamine andalcohol and heated on the water-bath until the evolution of ammonia ceases. 'Ihe solution thus formed is filtered, the solvent is distilled and the residue recrystallized from little alcohol. The 2 [2' -methoxy phenoxy -methyl] imidazoline hydrochloride of the formula NH- Hg OCH:

is thus obtained in the form of colorless crystals of melting point 167-169 C. The iminoether may also be produced in the presence of a solvent such as alcohol, ether, benzene, petroleum ether,

chloroform, or ethylene dichloride.

Instead of hydrogen chloride there may be used other mineral acids, for instance hydrobromic acid or sulfuric acid. In like manner, instead of ethyl alcohol there may be used other alcohols,

i for example methyl alcohol or butyl alcohols.

In similar manner there may be produced other 2- [phenoxy-alkyll-imidazolines, for example 2- [phenoxy-methy1l, 2-[phenoxy-propyl]-, 2- [phenoxy-hexyll-, 2-[a-phenoxy-hexyl-(t)-]-, 2- [-hydroxy-phenoxy-alhl] 2- [alkoxy-phenoxy-alkyllsuch as 2- [butyloxy-phenoxy-alkyll-imidazolines.

Example 2 Hydrogen chloride is introduced into the cooled chloroform solution of equimolecular quantities of alcohol and thymoxy-acetonitrile (of boiling point 118 C. under 0.8 mm. pressure obtained for example from thymol and chloroaceto nitrile in the presence of an acid binding agent). After some hours the solvent is distilled. The thymoxyacetiminoether-hydrochloride thus formed of the formula is left as a crystalline mass.

27 parts of this iminoether-hydrochloride are mixed with 6.5 parts of ethylene diamine and alcohol and heated on the water-bath until the evolution of ammonia ceases. The alcoholic so lution is filtered, evaporated to dryness and the residue is boiled with acetone whereby the 2- [thymow-methyl] -imidazoline-hydrochloride of the formula thus formed is left as a colorless crystalline powder of melting point 215-217 C. It is easily soluble in water.

Other 2- [phenoxy-alkyl] -imidazolines alkylated in the phenyl nucleus, such as for example 2'-, 3'- or 4'-methyl-, and 2'-metbyl-5'-isopropyl-, 4'-propenyl-, 2-methoxy-4'-allyl-, 2- methoxy-6'-allyl- (phenoxy-methyl) (phenoxypropyl) or -(phenoxy-butyl) -imidazolines may be obtained according to the same process.

Example '3 A solution of 10 parts of alcohol and 8 parts of hydrogen chloride in ether is mixed while 'cooling with 36.6 parts of a-naphthoxy-acetonitrile (of melting point 65 C. obtained for example by the actionof a-naphthol onchloro-aceto-nitrile in the presence of acid binding agents). The a-naphthoxyacetimino-ether hydrochloride of the formula thus obtained crystallizes after a short time in the form of colorless crystals. 26.5 parts of this compound are mixed with 6.5 parts of ethylene diamine dissolved in alcohol and heated on the water-bath for several hours. The solution which is filtered hot precipitates colorless crystals on cooling which may be recrystallized from little water. The new compound, i. e. the 2- [naphthoxy- (1') -methyl] -imidazoline-hydrochloride of the formula N-OH,

oomc .1101

NH- Hg 2- [phenoxy-methyl] imidazoline hydrochloride of melting point -132 C.

2- [2'-ethoxy-phenoxy-methyll -imidazoline hy drochloride of melting point 138139 C.

2- [6-al1yl-2'-methoxy-phenoxy-methyl] -imidazoline-hydrochloride of melting point 128 C.

2- [4'-allyl -2 -methoxy-phenoxy-methyl] -imidazoline-hydrochloride of melting point 152-153 2- [4 '-methoxy-phenoxy-methyl] -imidazoline-hydrochloride of melting point 89-90 C.

2- [phenoxy-propyl] -imidazoline-h.vdrochloride of melting point 139-140" C. i

2- [2'-methoxy-phenoxy-propyl] -imidazoline-hydrochlorideof melting point 166 C.

2- [6'-a1lyl-2'-methoxy-PhenoXy-Propyl]-imidaz- 1 oline picrate of melting point 189-190 C.

. 2- [2-phenoxy- (1') -methyl]-imidazo1ine-hydro- 2. The compounds 0! the formula chloride of melting point 198-200 C.

2- [naphthoXy-(2) -methyl] -im1da,zoline hydrochloride of melting point 206 C. 0-0m-0 5 2- [qulnolyl-(B') -oxy-methyl]-lmida.zoline-hydroxo H 5 chloride of melting point 191 C.

What I claim is: 1. The compounds of the formula wherein X stands for M1. 3. The compoundo of the formula 10 10 R-O-(CH!)n-O N-.-om

z o0H,o 1 wherein R stands for a, member of the group consisting of substituted and unsubstituted phenyl, 0X r naphthyl and quinolyl radicals, the substituent being a. member of the group consisting of alkyl, wherein 3 stands g s? alkenyl, hydrow and alkoxy and 7; stands for the mm 30 numbers 1 to 6. 

